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Atul Butte's presentation at the From Data to Discovery symposium at Westat
1. From a Trillion Points of Data into
Discoveries, Diagnostics, and
New Insights in Health and Disease
atul.butte@ucsf.edu
@atulbutte
Atul Butte, MD, PhD
Director, Bakar Computational
Health Sciences Institute
Distinguished Professor of Pediatrics, UCSF
Chief Data Scientist, University of California Health
13. 227 million substances x
1.3 million assays
More than a billion measurements
within a grid of 300 trillion cells
71 million meet Lipinski 5
1.2 million active substances
17. Credit: Stanford Lane Medical Library and Google Books
39 Cancer of the buccal cavity
40 Cancer of stomach and liver
41 Cancer of peritoneum, intestines, rectum
...
44 Cancer of skin
45 Cancer of other organs or
not specified
Lung is an âother organâ
Brain is an âother organâ
...
189 Visitation from God
25. Preeclampsia: large cause of maternal and fetal death
⢠Incidence
⢠5-8% of all pregnancies in the U.S. and worldwide
⢠4.1 million births in the U.S. in 2009
⢠Up to 300K cases of preeclampsia annually in the U.S.
⢠Mortality
⢠Responsible for 18% of all maternal deaths in the U.S.
⢠Maternal death in 56 out of every 100,000 live births in US
⢠Neonatal death in 71 out of every 100,000 live births in US
⢠Cost
⢠$20 billion in direct costs in the U.S. annually
⢠Average hospital stay of 3.5 days
Linda Liu
Bruce Ling
Matt Cooper
26.
27. New blood markers for preeclampsia
Linda Liu
Bruce Ling
Matt Cooper
@MarchofDimes
bit.ly/preeclamp
28. Need a
diagnostic for
preeclampsia
Public big data
available
March of Dimes
Center for
Prematurity
Research
Data analyzed,
diagnostic
designed
SPARK grant
($50k)
Life Science
Angels, other
seed investors
($2 million)
@CarmentaBio
progenity.com
bit.ly/carm_prog
31. Joel Dudley
Marina Sirota
Rat colonoscopy Rat model of
Inflammatory
Bowel Disease
Inflammatory Bowel
Disease
After Topiramate
Science Translational Medicine 2011, bit.ly/scitmtop
Anti-epileptic drug topiramate works against a
rat model of inflammatory bowel disease
32. Cancer Discovery 2013, 3:1.
Psychiatric Drug Imipramine Shows Significant Activity
Against Small Cell Lung Cancer
Vehicle control Imipramine
p53/Rb/p130
triple knockout
model of SCLC
Mice dosed after
tumor formation
Joel Dudley
Nadine Jahchan
Julien Sage
Alejandro Sweet-Cordero
Joel Neal
@NuMedii
35. Need more drugs
for more diseases
Public big data
available
NIH funding
Data analyzed,
method designed
Company launched,
ARRA, StartX,
Stanford license,
first deal
Claremont Creek,
Lightspeed ($3.5
million)
@NuMedii
36. The next big open data: clinical trials
Download 300+ studies today
Drug repositioning, new patient subsets,
digital comparative effectiveness, more!
immport.org
Sanchita Bhattacharya
Elizabeth Thomson
37. ImmPort redistributes data from
major NIAID-funded programs and more
Data from 300+ trials and studies already released, involving:
⢠Immune Tolerance Network (ITN)
⢠Atopic Dermatitis Research Network (ADRN)
⢠Clinical Trials in Organ Transplantation (CTOT) and in Children (CTOT-C)
⢠Population Genetics Analysis Program
⢠Protective Immunity for Special Populations
⢠Human Immunology Project Consortium
⢠HLA Region Genomics in Immune-mediated Diseases
⢠Modeling Immunity for Biodefense
⢠Reagent Development for Innate Immune Receptors
⢠Adjuvant Development Program
⢠Innate Immune Receptors and Adjuvant Discovery Program
⢠Maintenance of Macaque Specific Pathogen-Free Breeding Colonies
⢠Non-human Primate Transplantation Tolerance Cooperative Study Group
Collaborations with The Bill and Melinda Gates Foundation and March of Dimes
and the NIH Accelerating Medicines Partnership (AMP)
De-identified raw clinical study data is released to the public along with genetic,
gene expression, and flow cytometry measurements, in open formats
Hundreds of user downloads per month
255 255
291 290 301 301 309 309 309 309 318 318 318
141 148
109 116 109 99 101 106 107 102 104 105
120
ImmPort Study Summary
Cumulative Number of DAIT-
funded studies shared
Cumulative Number of Private
Studies in ImmPort
40. Reanalyzing RAVE
⢠Rituximab in ANCA-Associated Vasculitis (RAVE) trial of new approach to
the induction of remission
â randomized
â double-blind
â double-dummy
â active-controlled
â non-inferiority
41.
42.
43. Reproduce CD19+ B-cell depletion
using publicly released clinical trials data
Nasrallah M, âŚ, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
44. RAVE re-analysis
⢠63 of the 99 patients in the rituximab group (64%) reached the
primary end point, as compared with 52 of 98 in the control group
(53%).
⢠The treatment difference of 11% points between the groups met the
criterion for non-inferiority (P<0.001).
In retrospect, do any measured factors
predict response?
Mazen Nasrallah
Nasrallah M, âŚ, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
45. Nasrallah M, âŚ, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
Granularity index higher in rituximab-treated
subjects with remission
SSC
1 2
Granulocyte Subpopulations and Treatment Outcomes
Panel A: representative bi-dimensional dot-plot of granulocyte sub-
populations identified by ImmPortFLOCK on the basis of FSC and SSC.
A1: Hypogranular granulocytes with an SSC of low or positive (2 or 3).
A2: Hyper granular granulocytes with an SSC of high (4).
Panel B: granularity index at day 0 among patients receiving rituximab or
cyclophosphamide, stratified by treatment outcome (failure: red,
success: blue). Data distribution is shown as a boxplot, with mean Âą
SEM represented by dots and small error bars. CYC: cyclophosphamide,
RTX: rituximab. A Welch two-sided t-test was used to calculate
significance.
46. Nasrallah M, âŚ, Butte AJ. Arthritis Research & Therapy (2015) 17:262.
ANCA-
associated
Vasculitis
ProďŹled
Therapy
~ 54% of patients
Non-proďŹled
Therapy
~46% of patients
Treat with
Rituximab
~ 30% of patients
Remission Rate ~ 83%
Treat with
Cyclophosphamide
~24% of patients
Remission Rate ~ 66%
Do not treat with
Cyclophosphamide
Failure rate ~ 67%
Do not treat with
Rituximab
Failure rate ~ 70%
GI ⤠-9.25%
OR
GI ⼠47.6%
GI ⤠-9.25% GI ⼠47.6%
Treat with either Rituximab or
Cyclophosphamide
according to best clinical judgement
Average Remission Rate ~ 60%
Non-proďŹled
Therapy
100% of patients
NO
Proposed
Method
Current
Method
Measure the Granularity Index
(GI)
YES
Mazen Nasrallah
51. ⢠Founded 2015
⢠49 affiliated faculty members from UCSFâs four
top-ranked schools
â 5 in National Academy of Medicine
â 1 in National Academy of Science
â 2 in the American Society for Clinical Investigation
â 3 NIH Directorâs Awards
â 2 Sloan Foundation fellows
â 1 HHMI faculty scholar
â 1 MacArthur Foundation fellow
â 1 Chan/Zuckerberg faculty fellow
52. Build the strongest team in the world in
biomedical computation and health data analytics
⢠Academic affinity home for faculty and staff
⢠Research and development (and spin out technologies)
⢠Develop new educational plans
⢠Bring the best new computational and informatics faculty members
to UCSF
⢠Organize infrastructure and operations
⢠Build and use our new data assets for precision medicine
53. University of California
⢠10 campuses and 3 national labs
⢠~200,000 employees, ~250,000 students/yr
UC Health
⢠18 health professional schools (6 med schools)
⢠Train half the medical students and residents in
California
⢠~$2 billion NIH funding
⢠$11.4 billion clinical operating revenue
⢠5000 faculty physicians, 12000 nurses
⢠UCSF and UCLA are in US News top 10
⢠5 NCI Comprehensive Cancer Centers, 5 NIH CTSA
54. UC Health Data Analytics Platform
Combining healthcare data from across the
six University of California medical schools and systems
Health Data Warehouse
69. Predicting the disease before it strikes
Explaining the rare disease that defies experts
Finding drugs for diseases lacking attention
Making sure we do the right thing for patients
An amazing platform for biomedical innovation
Big Data in Biomedicine isâŚ
71. UC Clinical Data Warehouse Team
Executive Team
⢠Atul Butte
⢠Joe Bengfort
⢠Michael Pfeffer
⢠Tom Andriola
⢠Chris Longhurst
Steering Committee
⢠Lisa Dahm
⢠Mohammed Mahbouba
⢠David Dobbs
⢠Kent Andersen
⢠Ralph James
⢠Jennifer Holland
⢠Eugene Lee
ETL Team
⢠Albert Dugan
⢠Tony Choe
⢠Michael Sweeney
⢠Timothy Satterwhite
⢠Ayan Patel
⢠Niranjan Wagle
⢠Ralph James
⢠Joseph Dalton
Data Harmonization
⢠Dana Ludwig
⢠Daniella Meeker
Data Quality
⢠Momeena Ali
⢠Jodie Nygaard
Business Analyst
⢠Ankeeta Shukla
Hardware
⢠Sandeep Chandra
⢠Jeff Love
⢠Scott Bailey
⢠Kwong Law
⢠Pallav Saxena
Support
⢠Elizabeth Engel
⢠Jack Stobo
⢠Michael Blum
⢠Sam Hawgood
72. Collaborators
⢠Alejandro Sweet-Cordero, Julien Sage /
Pediatric Oncology
⢠Elizabeth Thomson, Patrick Dunn / Northrop
Grumman
⢠Gabe Rosenfeld, Quan Chen / NIAID
⢠Andrei Goga / UCSF Oncology
⢠Mallar Bhattacharya / UCSF Pulmonary
⢠Minnie Sarwal / UCSF Nephrology
⢠Geoffrey Gurtner / UCSF Surgery
⢠Roberta Diaz Brinton / Arizona
⢠Carol Bult / Jackson Labs
⢠David Stevenson, Gary Shaw / Stanford
Neonatology
⢠Takashi Kadowaki, Momoko Horikoshi, Kazuo
Hara, Hiroshi Ohtsu / U Tokyo
⢠Kyoko Toda, Satoru Yamada, Junichiro Irie /
Kitasato Univ and Hospital
⢠Shiro Maeda / RIKEN
⢠Mark Davis, C. Garrison Fathman /
Immunology
⢠Russ Altman, Steve Quake / Stanford
Bioengineering
⢠Euan Ashley, Joseph Wu / Stanford Cardiology
⢠Mike Snyder, Carlos Bustamante, Anne Brunet
/ Stanford Genetics
⢠Jay Pasricha / Stanford Gastroenterology
⢠Rob Tibshirani, Brad Efron / Stanford Statistics
⢠Hannah Valantine, Kiran Khush/ Stanford
Cardiology
⢠Mark Musen, Nigam Shah / National Center for
Biomedical Ontology
⢠Sam So, Ken Weinberg, David Miklos /
Stanford Oncology
73. Support
Admin and Tech Staff
⢠Mary Lyall
⢠Mounira Kenaani
⢠Kevin Kaier
⢠Boris Oskotsky
⢠Mae Moredo
⢠Ada Chen
⢠University of California, San Francisco
⢠Priscilla Chan and Mark Zuckerberg
⢠NIH: NIAID, NLM, NIGMS, NCI, NHLBI, OD; NIDDK, NHGRI, NIA, NCATS, NICHD
⢠California Governorâs Office of Planning and Research
⢠March of Dimes
⢠Juvenile Diabetes Research Foundation
⢠Howard Hughes Medical Institute, California Institute for Regenerative Medicine
⢠Hewlett Packard, LâOreal, Progenity
⢠Scleroderma Research Foundation
⢠Clayville Research Fund, PhRMA Foundation, Stanford Cancer Center, Bio-X, SPARK
⢠Tarangini Deshpande
⢠Kimayani Butte
⢠Talmadge King and Mark Laret
⢠Sam Hawgood and Keith Yamamoto
⢠Isaac Kohane